Notch signalling at the crossroads of T cell development and leukemogenesis

Members of the Notch family (e.g. Notch1 and Notch3) have been recently described to play a critical role in T cell development and their constitutive activation has been related to T cell leukaemia in both animal models and human disease. Nevertheless, whether they act as redundant molecules, by affecting the same molecular mechanisms, or play distinct roles in T cell differentiation and/or leukemogenesis is not clear. Altered Notch signalling impairs the developmentally-regulated interplay between pre-TCR signalling, NFkappaB and E2A activities, thus identifying the crucial role of Notch receptors at the cross-roads of disrupted lymphoid differentiation and neoplastic transformation.